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DE3687543T2 - MEASURING PROBE FOR BIOLOGICAL MOLECULES WITH USE OF OPTICAL WAVE GUIDE. - Google Patents

MEASURING PROBE FOR BIOLOGICAL MOLECULES WITH USE OF OPTICAL WAVE GUIDE.

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Publication number
DE3687543T2
DE3687543T2 DE8686302650T DE3687543T DE3687543T2 DE 3687543 T2 DE3687543 T2 DE 3687543T2 DE 8686302650 T DE8686302650 T DE 8686302650T DE 3687543 T DE3687543 T DE 3687543T DE 3687543 T2 DE3687543 T2 DE 3687543T2
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waveguide
medium
light
coating
biosensor according
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DE3687543D1 (en
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William James Stewart
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Marconi UK Intellectual Property Ltd
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Marconi Co Ltd
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/808—Optical sensing apparatus
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/805—Optical property

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Plasma & Fusion (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

An optic-waveguide biosensor (fig 2) of the type comprising an optic-waveguide (1) provided with a coating (7) sensitized to a specific assay species, and input and output coupling members (3) and (5). Light signal response is enhanced by incorporating a partially reflecting, partially transmitting, low refractive index medium (15) between each coupling member (3,5) and the waveguide (1). The thickness of this medium (15) is chosen so that light may be coupled by frustrated total internal reflection and so that the medium (15) serves as a resonant mirror. It may be in the form of a single layer (fig 3(a)) formed of eg. magnesium fluoride or alumina material. Alternatively, it may be of multilayer structure dielectric material (fig 3 (b)).

Description

Die vorliegende Erfindung betrifft Meßfühler für biologische Moleküle (kurz Biosensoren) mit Verwendung optischer Wellenleiter, d. h. Sensoren zum Erfassen und/oder Überwachen oder zur quantitativen Bestimmung des Vorhandenseins und/oder Verhaltens spezifischer molekularer Testgattungen in Testfluidproben. Die Erfindung weist beispielsweise folgende Anwendung auf: Immunitätsprüfung (die Detektion von Antikörpern, Antigenen oder Hormonen in Blutproben), Verunreinigungsüberwachung; und Überwachung klinischer diagnostischer Reaktionen, die z. B. Enzyme und dergleichen umfassen.The present invention relates to biological molecule sensors (biosensors) using optical waveguides, i.e. sensors for detecting and/or monitoring or quantifying the presence and/or behavior of specific molecular test species in test fluid samples. The invention has, for example, application in: immunity testing (the detection of antibodies, antigens or hormones in blood samples), contamination monitoring; and monitoring of clinical diagnostic reactions involving, for example, enzymes and the like.

In einem Artikel mit dem Titel "Detection of Antibody-Antigen Reactions at a glass-Liquid Interface as a Novel Optical Immunoassay Concept" (1984) (Proceedings der 2ten Optischen Wellenleitertagung (Stuttgart 1984) Seite 75) beschreiben R.M. Sutherland et al einen Biosensor, in dem eine Antikörpergattung kovalent auf der Oberfläche eines planaren oder faseroptischen Wellenleiters immobilisiert wird. Die Reaktion des immobilisierten Antikörpers mit Antigen in Probenlösung wird unter Ausnutzung der Dämpfungs- oder Evaneszenzwellenkomponente eines Lichtstrahls, der viele Male innerhalb des Wellenleiters intern total reflektiert worden ist, erfaßt. Die evanesente Welle weist eine charakteristische Eindringtiefe eines Bruchteils einer Wellenlänge in die wässrige Phase auf, so daß sie optisch mit Substanzen, die an die Grenzschicht angebunden sind oder sehr dicht an dieser liegen, und nur minimal mit der Hauptlösung wechselwirkt.In an article entitled "Detection of Antibody-Antigen Reactions at a glass-Liquid Interface as a Novel Optical Immunoassay Concept" (1984) (Proceedings of the 2nd Optical Waveguide Conference (Stuttgart 1984) page 75) R.M. Sutherland et al describe a biosensor in which an antibody species is covalently immobilized on the surface of a planar or fiber optic waveguide. The reaction of the immobilized antibody with antigen in sample solution is detected by utilizing the attenuation or evanescent wave component of a light beam that has been totally internally reflected many times within the waveguide. The evanescent wave has a characteristic penetration depth of a fraction of a wavelength into the aqueous phase, so that it optically interacts with substances that are bound to the boundary layer or are very close to it, and only minimally with the bulk solution.

Es wird auch auf die Britische Patentanmeldung GB-A-2156970 verwiesen, die optisches Wellenleiter-Biosensoren und eine ähnliche Technik offenbart.Reference is also made to British Patent Application GB-A-2156970, which discloses optical waveguide biosensors and similar technology.

In "Analytical Chemistry", Band 54, Nr.9, August 1982, Seiten 1071-1080, ist eine Technik zur Analyse einer Filmbeschichtung beschrieben, in der Licht über Prismen in einen optischen Körper, auf dem die Beschichtung ausgebildet ist, hineingekoppelt und aus diesem herausgekoppelt wird.In "Analytical Chemistry", Volume 54, No. 9, August 1982, pages 1071-1080, a technique for analyzing a film coating is described in which light is coupled into and out of an optical body on which the coating is formed via prisms.

Die vorliegende Erfindung dient dazu, die Antwort der Vorrichtung für eine gegebene Strahlleistung anzuheben.The present invention serves to increase the response of the device for a given beam power.

Gemäß der Erfindung ist ein Meßfühler für biologische Moleküle mit Verwendung optischer Wellenleiter vorgesehen, der einen Wellenleiter, welcher eine Grenzfläche mit einer Beschichtung aufweist, die für eine gegebene Testgattung sensibilisiert ist, wobei der Wellenleiter einen höheren Brechungsindex als die Beschichtung aufweist, und zwei Lichtkopplungsteile angrenzend an den Wellenleiter umfaßt, die Licht in den Wellenleiter hinein- bzw. herauslenken, dadurch gekennzeichnet, daß der Biomeßfühler ein dielektrisches Festkörpermedium umfaßt, das zwischen dem Wellenleiter und einem oder beiden dieser Kopplungsteile angeordnet ist und eine Licht reflektierende und teilweise durchlässige Grenzfläche mit dem Wellenleiter und eine Grenzfläche mit diesem einen oder beiden Kopplungsteilen aufweist; daß der Wellenleiter einen solchen Brechungsindex in Relation zu diesem Medium aufweist, daß der Wellenleiter und die Grenzflächen des Wellenleiters mit der Beschichtung und mit dem Medium gemeinsam einen verspiegelten Resonanzhohlraum bilden.According to the invention there is provided a biological molecule sensor using optical waveguides comprising a waveguide having an interface with a coating sensitized to a given test species, the waveguide having a higher refractive index than the coating, and two light coupling members adjacent to the waveguide directing light into and out of the waveguide, respectively, characterized in that the biosensor comprises a solid dielectric medium disposed between the waveguide and one or both of said coupling members and having a light-reflecting and partially transmissive interface with the waveguide and an interface with said one or both of said coupling members; that the waveguide has a refractive index relative to said medium such that the waveguide and the interfaces of the waveguide with the coating and with the medium together form a mirrored resonant cavity.

Die Strahlungsleistung innerhalb des Hohlraums wird so in Bezug auf die Eingangsstrahlleistung gesteigert und die Leistung der interaktiven evaneszenten Welle, die sich in die sensibilisierte Beschichtung erstreckt, wird gleichermaßen gesteigert, wodurch die Empfindlichkeit der Vorrichtung gegenüber durch die Beschichtung absorbierter Gattungen verbessert wird.The radiation power within the cavity is thus increased in relation to the input beam power and the power of the interactive evanescent wave, which is in the sensitized coating is similarly increased, thereby improving the sensitivity of the device to species absorbed by the coating.

Das dielektrische Festkörpermedium kann eine einzige Schicht aus transparentem Material sein. Alternativ kann es eine dielektrische Mehrfachschichtstruktur sein.The solid-state dielectric medium may be a single layer of transparent material. Alternatively, it may be a multilayer dielectric structure.

In den beiliegenden ZeichnungenIn the attached drawings

ist Fig. 1 eine illustrative Querschnittsansicht eines bekannten optischen Wellenleiter-Biosensors;Fig. 1 is an illustrative cross-sectional view of a known optical waveguide biosensor;

ist Fig. 2 eine illustrative Querschnittsansicht eines optischen Wellenleiter-Biosensors, der gemäß der Erfindung modifiziert ist; undFig. 2 is an illustrative cross-sectional view of an optical waveguide biosensor modified according to the invention; and

zeigt Fig. 3 in schematischer Weise Brechungsindexprofile für einen modifizierten Biosensor, derFig. 3 shows schematically refractive index profiles for a modified biosensor, which

a) einen Einzelschichtreflektor; bzw.a) a single layer reflector; or

b) einen Reflektor mit mehrschichtigem Aufbau enthält.b) contains a reflector with a multi-layer structure.

Ausführungsbeispiele der Erfindung werden nun lediglich beispielhalber unter Bezug auf die der Beschreibung beigefügten Zeichnungen beschrieben.Embodiments of the invention will now be described by way of example only with reference to the drawings accompanying the description.

In Fig. 1 ist die Form eines optischen Wellenleiter-Biosensors gezeigt, der in dem zuvor erwähnten Artikel von R.M Sutherland et al offenbart ist, in welchem Sensor Licht von einer Quelle S mittels eines ersten Kopplungsprismas 3 in einen ebenen Wellenleiter 1 gerichtet wird und sich durch mehrfache interne Totalreflexion zum Austritt mittels eines zweiten Kopplungsprismas 5 ausbreitet, von wo aus es in einen Lichtdetektor D geleitet wird. Die äußere Oberfläche des Wellenleiters 1 ist mit einer sensibilisierten organischen Beschichtung 7 versehen. Letztere ist einer Probenflüssigkeit 9 ausgesetzt, die in einer Anordnung mit Strömungszelle 11 und Dichtung 13 enthalten ist. In der Beschichtung 7 ist Antikörpermaterial kovalent immobilisiert und dies spricht auf jedwedes spezifisches Antigenmaterial in der Probenflüssigkeit an, der es ausgesetzt ist. Der Wellenleiter besteht aus geschmolzenem Quarzmaterial und dies sorgt für eine großes Differential in der optischen Dichte zwischen dem Quarzwellenleiter 1 (hohen Brechungsindex n&sub1;) und der angrenzenden Beschichtung 7 (geringen Brechungsindex n&sub2;). Licht wird innerhalb des Körpers vom Wellenleiter 1 intern total reflektiert, ein Teil der optischen Leistung breitet sich jedoch als eine evaneszente Welle im Beschichtungsmedium 7 aus. Die Antigenbindung durch den immobilisierten Antikörper wird durch eine resultierende Zunahme der Lichtabsorption überwacht, die vom Detektor D gemessen wird.In Fig. 1 is shown the form of an optical waveguide biosensor disclosed in the aforementioned article by RM Sutherland et al, in which sensor light from a source S is directed into a plane waveguide 1 by means of a first coupling prism 3 and propagates by multiple total internal reflection to the exit by means of a second coupling prism 5, from where it is directed into a light detector D. The outer surface of the waveguide 1 is provided with a sensitized organic coating 7. The latter is exposed to a sample liquid 9 contained in an arrangement with flow cell 11 and seal 13. In the Coating 7 has antibody material covalently immobilized and this responds to any specific antigen material in the sample fluid to which it is exposed. The waveguide is made of fused quartz material and this provides a large differential in optical density between the quartz waveguide 1 (high refractive index n1) and the adjacent coating 7 (low refractive index n2). Light is totally internally reflected from the waveguide 1 within the body, but some of the optical power propagates as an evanescent wave in the coating medium 7. Antigen binding by the immobilized antibody is monitored by a resulting increase in light absorption which is measured by detector D.

In der in Fig. 2 gezeigten erfindungsgemäßen Modifikation ist eine Schicht 15 (beispielsweise eine aufgedampfte oder aufgesputterte Schicht aus Magnesiumfluorid) zwischen die Kopplungsprismen 3,5 und den planaren Wellenleiter 1 eingefügt. Die Schicht 15 weist einen geringeren Brechungsindex auf als der Wellenleiter 1 und die Grenzfläche zwischen der Schicht 15 und dem Wellenleiter 1 ist lichtreflektierend und teilweise durchlässig. Dieser Aufbau kann in Verbindung mit einem Infrarotlicht-Injektionslaser als Lichtquelle S mit einer typischen Wellenlänge von 0,8 um verwendet werden. Ein ähnlicher Apparat kann für sichtbares Licht und für ultraviolettes Licht verwendet werden, wobei jedoch in letzterem Fall eine Schicht 15 aus Aluminiumoxid oder ähnlichem Material verwendet würde, wobei die typische Wellenlänge 270 nm beträgt. Licht wird in den Wellenleiter 1 durch behinderte interne Totalreflexion (interne FTR von Frustrated Total Reflection) gekoppelt und die Dicke der zwischengefügten Schicht 15 wird entsprechend gewählt. Das Brechungsindexprofil für diese Anordnung von MedienIn the modification according to the invention shown in Fig. 2, a layer 15 (for example a vapor-deposited or sputtered layer of magnesium fluoride) is inserted between the coupling prisms 3, 5 and the planar waveguide 1. The layer 15 has a lower refractive index than the waveguide 1 and the interface between the layer 15 and the waveguide 1 is light-reflecting and partially transmissive. This structure can be used in conjunction with an infrared light injection laser as the light source S with a typical wavelength of 0.8 µm. A similar apparatus can be used for visible light and for ultraviolet light, but in the latter case a layer 15 of aluminum oxide or similar material would be used, the typical wavelength being 270 nm. Light is coupled into the waveguide 1 by Frustrated Total Reflection (FTR) and the thickness of the interposed layer 15 is chosen accordingly. The refractive index profile for this arrangement of media

- Beschichtung 7, Wellenleiter 1, Schicht 15 und Kopplungsteil 3 - ist in Fig. 3(a) gezeigt. Wie dort ersichtlich ist, ist der Wellenleiter 1 durch die Medien 7, 15 geringeren Brechungsindex isoliert. Einfallendes, in den Wellenleiter eingekoppeltes Licht wird daher resonant im verspiegelten Hohlraum zwischen den Grenzflächen des Wellenleiters 1 mit der Schicht 15 und der Beschichtung 7 eingefangen. Der Leistungspegel ist in diesem Hohlraumbereich hoch. Der geführte Lichtstrahl zweigt darauffolgend zurück in das Grundmedium, das zweite Kopplungsteil 5, ab, wonach er durch den Fotodetektor D aufgenommen wird. Die evaneszente Welle in der Beschichtung 7 wird mit jedweder in dieser Beschichtung 7 absorbierter Gattung wechselwirken und wird daher dann wiederum die Absorption und Phasenschiebung des aufgenommenen Lichtstrahls modifizieren. Letztere Komponente wird durch diesen Resonanzeffekt verstärkt.- coating 7, waveguide 1, layer 15 and coupling part 3 - is shown in Fig. 3(a). As can be seen there, the waveguide 1 is through the media 7, 15 lower refractive index. Incident light coupled into the waveguide is therefore resonantly captured in the mirrored cavity between the interfaces of the waveguide 1 with the layer 15 and the coating 7. The power level is high in this cavity region. The guided light beam subsequently branches off back into the base medium, the second coupling part 5, after which it is received by the photodetector D. The evanescent wave in the coating 7 will interact with any species absorbed in this coating 7 and will therefore in turn modify the absorption and phase shift of the received light beam. The latter component is amplified by this resonance effect.

Als eine alternative Modifikation kann die zwischengefügte einzelne Schicht 15 der in Fig. 2 gezeigten Anordnung durch eine dielektrische mehrschichtige Struktur 15' ersetzt werden. Ein typisches Indexprofil für diese modifizierte Anordnung ist in Fig. 3(b) gezeigt. Als Beispiel liefert eine mehrschichtige Struktur, die 90% Reflexion und 10% Transmission vorsieht, einen Faktor x10 an Leistungssteigerung innerhalb des Resonanzhohlraums.As an alternative modification, the interposed single layer 15 of the arrangement shown in Fig. 2 can be replaced by a dielectric multilayer structure 15'. A typical index profile for this modified arrangement is shown in Fig. 3(b). As an example, a multilayer structure providing 90% reflection and 10% transmission provides a factor of x10 of power enhancement within the resonant cavity.

Das Vorhandensein der Prüf- oder Testgattung kann durch Messen der Änderungen in der Absorption oder Polarisation des aufgenommenen Lichtstrahls erfaßt und/oder überwacht werden. Die Wechselwirkung wird von der Frequenz und dem Einfallswinkel des Lichtstrahls abhängen. Die Quelle S und der Detektor D können singuläre Komponenten sein, die mechanisch über einen Bereich von Winkeln gescannt werden, oder können jeweils eine ausgedehnte Anordnung umfassen, wobei jede Komponente zur Simulierung einer Abtastung elektronisch adressiert wird. Alternativ können die Quelle und der Detektor D in einer statischen optischen Konfiguration angeordnet sein.The presence of the test species can be detected and/or monitored by measuring the changes in the absorption or polarization of the received light beam. The interaction will depend on the frequency and angle of incidence of the light beam. The source S and detector D can be singular components that are mechanically scanned over a range of angles, or can each comprise an extended array, with each component electronically addressed to simulate scanning. Alternatively, the source and detector D can be arranged in a static optical configuration.

Claims (6)

1. Meßfühler für biologische Moleküle mit Verwendung optischer Wellenleiter, aufweisend einen Wellenleiter (1), der eine Grenzfläche mit einer Beschichtung (7) aufweist, die für eine gegebene Prüfgattung sensibilisiert ist, wobei der Wellenleiter (1) einen höheren Brechungsindex als die Beschichtung (7) aufweist, und zwei an den Wellenleiter angrenzende Lichtkopplungsteile (3,5), die Licht in den Wellenleiter (1) hinein- bzw. herausleiten, dadurch gekennzeichnet, daß der Biomeßfühler ein dielektrisches Festkörpermedium (15,15') umfaßt, das zwischen dem Wellenleiter (1) und einem oder beiden Kopplungsteilen (3,5) angeordnet ist und eine lichtreflektierende und teilweise durchlässige Grenzfläche mit dem Wellenleiter (1) und eine Grenzfläche mit einem oder beiden Kopplungsteilen (3,5) aufweist; daß der Wellenleiter (1) einen derartigen Brechungsindex in Bezug auf dieses Medium (15,15') aufweist, daß der Wellenleiter und die Grenzflächen des Wellenleiters (1) mit der Beschichtung (7) und mit diesem Medium (15,15') gemeinsam einen verspiegelten Resonanzhohlraum bilden.1. A sensor for biological molecules using optical waveguides, comprising a waveguide (1) having an interface with a coating (7) sensitized to a given type of test, the waveguide (1) having a higher refractive index than the coating (7), and two light coupling parts (3, 5) adjacent to the waveguide which guide light into and out of the waveguide (1), characterized in that the biosensor comprises a dielectric solid medium (15, 15') arranged between the waveguide (1) and one or both coupling parts (3, 5) and having a light-reflecting and partially transmissive interface with the waveguide (1) and an interface with one or both coupling parts (3, 5); that the waveguide (1) has a refractive index in relation to this medium (15, 15') such that the waveguide and the interfaces of the waveguide (1) together with the coating (7) and with this medium (15, 15') form a mirrored resonance cavity. 2. Biomeßfühler nach Anspruch 1, in welchem das dielektrische Festkörpermedium eine einzelne Schicht (15) aus solchem Material und solcher Dicke umfaßt, daß eine Lichtkopplung durch behinderte interne Totalreflexion mit dem Wellenleiter (1) zustande kommt.2. A biosensor according to claim 1, in which the solid-state dielectric medium comprises a single layer (15) of such material and thickness that light coupling by obstructed total internal reflection with the waveguide (1) is achieved. 3. Biomeßfühler nach Anspruch 2, in welchem die einzelne Schicht (15) aus Magnesiumfluoridmaterial besteht.3. A biosensor according to claim 2, in which the single layer (15) consists of magnesium fluoride material. 4. Biomeßfühler nach Anspruch 2, in welchem die einzelne Schicht (15) aus Aluminiumoxidmaterial besteht.4. A biosensor according to claim 2, in which the single layer (15) consists of alumina material. 5. Biomeßfühler nach Anspruch 1, in welchem das dielektrische Festkörpermedium eine dielektrische mehrschichtige Struktur (15') umfaßt.5. A biosensor according to claim 1, in which the solid-state dielectric medium comprises a dielectric multilayer structure (15'). 6. Biomeßfühler nach Anspruch 5, in welchem die mehrschichtige Struktur (15') 90% Reflexion und 10% Transmission liefert.6. Biosensor according to claim 5, in which the multilayer structure (15') provides 90% reflection and 10% transmission.
DE8686302650T 1985-04-12 1986-04-10 MEASURING PROBE FOR BIOLOGICAL MOLECULES WITH USE OF OPTICAL WAVE GUIDE. Expired - Fee Related DE3687543T2 (en)

Applications Claiming Priority (1)

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GB858509491A GB8509491D0 (en) 1985-04-12 1985-04-12 Optic waveguide biosensors

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DE3687543D1 DE3687543D1 (en) 1993-03-04
DE3687543T2 true DE3687543T2 (en) 1993-05-13

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US (1) US4857273A (en)
EP (1) EP0205236B1 (en)
JP (1) JPH07117486B2 (en)
AT (1) ATE84876T1 (en)
DE (1) DE3687543T2 (en)
GB (2) GB8509491D0 (en)

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